[The influence of melatonin on mutagenicity and antitumor action of cytostatic drugs in mice].
SHR mice received single injections of N-nitrosomethylurea (NMU, 50 mg/kg, i.p.), cyclophosphamide (CP, 200 mg/kg, i.p.) or 1,2-dimethylhydrazine (DMH, 15 mg/kg, s.c.) alone or in combination with melatonin (5 mg/kg, s.c.). For mutagenic study chromosome aberrations tests (ChA) in bone marrow cells and sperm head anomaly test (SHA) were used. Melatonin did not appear mutagenic in either of the tests and significantly reduced the level of ChA (%) from 16.9 +/- 1.6 (NMU), 13.7 +/- 3.5 (CP) and 8.7 +/- 0.3 (DMH) to 4.5 +/- 0.6, 4.3 +/- 0.9 and 5.6 +/- 0.2, respectively, (p < 0.05). Similarly, SHA frequency (%) under the melatonin influence was reduced from 18.6 +/- 0.4 (NMU), 17.7 +/- 0.4 (CP) and 10.0 +/- 0.5 (DVH) to 9.9 +/- 0.5, 6.1 +/- 0.3 and 7.5 +/- 0.2, respectively, (p < 0.05). Unlike in controls, exposure to melatonin in drinking water (20 mg/l, at night) or in injections (5 mg/kg, s.c.) alone or in combination with NMU or CP failed to influence subcutaneously-transplanted Ehrlich carcinoma growth. These findings suggest that melatonin reduced the mutagenicity of the cytostatic drugs without affecting their anti-tumor action.
Musatov
S A
SA
Acad. I.P.Pavlov State Medical University, St. Petersburg.
Rosenfeld
S V
SV
Togo
E F
EF
Mikheev
V S
VS
Anisimov
V N
VN
D019813:1,2-Dimethylhydrazine / Q000037:antagonists & inhibitors; D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001854:Bone Marrow Cells / Q000187:drug effects; D002869:Chromosome Aberrations; D003520:Cyclophosphamide / Q000037:antagonists & inhibitors; D008297:Male; D008550:Melatonin / Q000502:physiology*; D008770:Methylnitrosourea; D051379:Mice; D008815:Mice, Inbred Strains; D016296:Mutagenesis / Q000187:drug effects / Q000502:physiology*; D009153:Mutagens / Q000008:administration & dosage; D009374:Neoplasms, Experimental / Q000139:chemically induced / Q000235:genetics*; D013077:Sperm Head / Q000187:drug effects
D016588:Anticarcinogenic Agents; D000970:Antineoplastic Agents; D009153:Mutagens; D008770:Methylnitrosourea; D003520:Cyclophosphamide; D019813:1,2-Dimethylhydrazine; D008550:Melatonin
Vliianie melatonina na mutagennost' i protivoopukholevyĭ éffekt tsitostatikov u mysheĭ.